tbuckley/cabot-search huggingface dataset:
PB2297: PHASE II STUDY OF BORTEZOMIB, CYTARABINE, AND DEXAMETHASONE IN RELAPSED OR REFRACTORY MANTLE CELL LYMPHOMA
Authors: Junghoon Shin, Ji Yun Lee, Gyeong-Won Lee, Won Seog Kim, Yong Park, Young Rok Do, Dae Sik Kim, Ki Hwan Kim, Yoon Seok Choi, Youngil Koh
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin’s lymphoma with a generally aggressive, albeit heterogeneous, clinical course. Cytarabine is a highly active antimetabolic agent included in aggressive induction chemotherapies for MCL, and bortezomib shows significant anti-MCL activity as a single agent or as a component of combination regimens. Aims: To evaluate the efficacy and safety of bortezomib, cytarabine, and dexamethasone (VAD) in patients with RRMCL. Methods: In this multicenter phase II study, we evaluated the clinical efficacy and safety of bortezomib, cytarabine, and dexamethasone (VAD) as a second to fourth-line treatment for relapsed or refractory MCL. Patients who had been treated with bortezomib previously or cytarabine within 6 months before enrollment were excluded. The primary endpoint was the investigator-assessed objective metabolic response rate. Results: From October 2015 to March 2021, 19 patients were enrolled across 9 teaching hospitals in South Korea. The median age at enrollment was 70 (range, 52-80). Six (32%), four (21%), and nine (47%) patients received one, two, and three prior lines of chemotherapy, respectively. The objective metabolic response was achieved in 12 (63%) patients, including 5 (26%) complete and 7 (39%) partial metabolic responses. The median duration of response was 7.5 months. Among ten patients who received ibrutinib previously, one and three achieved CMR and PMR, respectively. With a median follow-up of 9.1 months, the median progression-free survival and overall survival were 6 months and not reached, respectively. Nearly 80% of patients experienced grade 3 or 4 adverse events, most of which were hematological with thrombocytopenia being the most common toxicity. Summary/Conclusion: VAD shows promising clinical efficacy in patients with relapsed or refractory MCL with manageable and predictable toxicity (BATMAN ClinicalTrials.gov number, NCT02840539). Keywords: Bortezomib, Mantle cell lymphoma, Cytarabine, Clinical trial
P1651: IMPACT OF NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AND MACROPHAGE ACTIVATION IN THE THROMBOTIC EVENTS IN COVID-19 PATIENTS
Authors: Irene Serrano-Gonzalo, Bárbara Menéndez-Jandula, Isidro Arévalo-Vargas, Ester Franco-García, Carlos Lahoz, Paz Latre, Laura López de Frutos, Ralf Köhler, Pilar Giraldo
Journal: HemaSphere (2023)
PB2321: THE EFFECT OF PRE-TREATMENT SERUM KINDLIN-3 ON HODGKIN AND NON-HODGKIN LYMPHOMAS: A SINGLE CENTER EXPERIENCE
Authors: Melike Keskin, Hanife Usta Atmaca, Istemi Serin, Osman Yokus
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Lymphomas are a heterogeneous group of malignancies of lymphocytes that develop as a result of abnormal clonal proliferation of B lymphocytes, T lymphocytes or natural killer cells. Kindlins are a group of focal adhesion proteins involved in the activation of integrins. It has three members as kindlin-1, kindlin-2, and kindlin-3. Kindlin-3 is a protein in the kindlin protein family that regulates the functions of integrins by binding to the cytoplasmic part of the integrin beta chain. The result of kindlin-mediated integrin activation and integrin-ligand binding is cell adhesion, proliferation and migration, extracellular matrix aggregation, cell survival, proliferation and differentiation. It is mainly synthesized from hematopoietic cells. The close relationship between integrins and cancer pathogenesis has led to the investigation of the role of kindlins in cancers. Aims: Our study was designed to evaluate the effect of serum kindlin-3 level on disease susceptibility, treatment response and febrile neutropenia in newly diagnosed non-Hodgkin (NHL) and Hodgkin lymphoma (HL) patients. Methods: Patients who applied to Istanbul Training and Research Hospital, Hematology Clinic between May 2021 and September 2021 were included in the study. Forty-five patients were diagnosed with lymphoma (NHL and HL); 2 patients were excluded from the study. At the time of diagnosis, blood samples were taken into gel serum tubes and then their serum samples were obtained by centrifugation and stored at -80 ℃. Results: Thirty-four NHL and 9 HL, a total of 43 patients (29 M and 14 F) and 41 healthy controls (16 M and 25 F) were included in the study. Serum kindlin-3 levels were compared between patients and healthy controls. The mean serum kindlin-3 level was found to be statistically higher in healthy controls compared to patients (patients: 2.9±4, healthy controls: 10.42±7, p<0.001). According to the ROC analysis, serum kindlin-3 cut-off of 2.928 was found to be a statistically significant parameter in predicting the disease (AUC: 0.905, 95% CI: 0.838-0.972, p<0.05). There was no statistically significant effect on patients’ interim or end-of-treatment response or development of febrile neutropenia during their follow-up. Summary/Conclusion: The results suggest that kindlin-3 molecule can be considered as a possible biomarker in the etiopathogenesis of lymphoma. Graphic1. The ROC analysis: Serum kindlin-3 cut-off of 2.928Keywords: Non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, Prognosis
PB2247: BURDEN OF SYMPTOMS AND SYMPTOM EXPERIENCE OF FILIPINO MYELOPROLIFERATIVE NEOPLASM PATIENTS: A QUALITATIVE PHENOMENOLOGICAL STUDY
Authors: Flordeluna Mesina, Teresita Dumagay
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Myeloproliferative neoplasms (MPN) are a heterogeneous group of disorders characterized by the cellular proliferation of one or more hematologic cell lines. Philadelphia-negative MPN patients such as Polycythemia Vera (PV), Essential Thrombocytosis (ET), or Myelofibrosis (MF) suffer a series of objective problems related to the disease activity which can affect their quality of life. Aims: This study aims to determine the symptoms and symptom experience of Filipino patients with MPN. In addition, explore the symptoms that may be unique in Filipino MPN patients. Methods: Qualitative research, phenomenological study; Key informant interview was conducted with Myeloproliferative neoplasm patients. Data analysis used thematic analysis consisting of reading, writing notes, describing, classifying transcripts according to categories and themes. Results: After comprehensive analysis of narratives and categorical aggregation, The meta-themes identified were 1) Symptom Experience and 2) Disease Perception. Three sub-themes were identified under Symptom Experience: a) Heterogenous and complex symptomatology; b) Dynamic symptoms; c) Living and gaining control of symptoms. There were three sub-themes under Disease Perception namely: a) Struggle with the concept of the disease; b) Anxiety and Uncertainty; c) Acceptance and hope. Summary/Conclusion: This study explored the symptoms and the experiences of Filipino patients living with MPN. Majority had heterogenous, co-occurring and dynamic symptoms, the most common of which is fatigue. They also reported more vascular symptoms (headache and dizziness) while fever was uncommon. These symptoms affected their overall productivity both at home and at work. Perceptions about the disease include difficulty in understanding the concept of the disease, anxiety/uncertainty and eventually acceptance of the disease and complications. Keywords: Myeloproliferative disorder, Quality of life
P390: ALLO-HSCT OR CHEMOTHERAPY FOR B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN THE FIRST COMPLETE REMISSION: IMPACT OF MRD AND IKZF1
Authors: Shiyu Deng, Jiawang Ou, Zihong Cai, Zicong Huang, Xiuli Xu, Bingqing Tang
Journal: HemaSphere (2023)

Background: With intensified pediatric-like therapy and genetic disease dissection, a markedly improved outcome in adults with B-cell acute lymphoblastic leukemia (B-ALL). Aims: In this new context, we aimed to reassess the value of risk factors and evaluate the role of allogeneic stem cell transplantation (allo-HSCT) and chemotherapy in the different risk group patients treated in the PDT-ALL-2016 trial after the first complete remission (CR1). Methods: We retrospectively analyzed the samples collected from patients with B-ALL enrolled in the PDT-ALL-2016 trial. We reassessed the value of risk factors and combined early molecular responses and IKZF1 deletion, we redefined the patients as a standard, intermediate, and high-risk group. Next, we aimed to evaluate the role of allogeneic stem cell transplantation (allo-HSCT) and chemotherapy in the three groups of patients treated in the PDT-ALL-2016 trial after CR1. Results: In all, 202 patients aged 12 to 81 years old were enrolled, and the analysis included one hundred and eighty-three patients aged with complete MRD and IKZF1 gene deletion information. Among them, 92 (50.3%) received a transplant in CR1.In HR and IR groups, allo-HSCT is strongly associated with higher 5-year overall survival（OS）and event-free survival（EFS） and lower cumulative incidence of relapse (CIR). In the SR group, the patients who received allo-HSCT versus chemotherapy showed no significant advantage in 5-year OS， EFS, and CIR. Summary/Conclusion: Our study shows that early MRD response and IKZF1 deletion, in contrast to conventional B-ALL risk factors, is an excellent tool to identify patients who may benefit from allo-HSCT or chemotherapy regimens in the context of intensified pediatric-like adult ALL therapy.Keywords: Complete remission, Minimal residual disease (MRD), Ikaros, B cell acute lymphoblastic leukemia
PB2241: THE VASCULAR RISK OF ESSENTIAL THROMBOCYTHEMIA AND RELIABILITY OF THROMBOTIC RISK ASSESSMENT SCORES
Authors: Arij Cheffai, Slama Nader, Ouahchi Ines, Laabidi Baraa, Wiem Boufrikha, Sarra Boukhriss, Adnene Laatiri
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Essential thrombocythemia (ET) is a Philadelphia negative myeloproliferative neoplasm. Although its prognosis is generally favorable, ET is associated with an inherent risk of various complications. However, its risk is essentially vascular, dominated by the occurrence of thrombosis. Therefore, the assessment of thrombotic risk at the time of diagnosis of ET is a crucial point for the therapeutic decision. Aims: We aimed to describe the incidence and locations of thrombotic and hemorrhagic complications of ET. We also studied the performance of different thrombotic risk scores in predicting the occurrence of thrombosis in our patients. Methods: This is a retrospective study of 74 patients followed up for ET in the Clinical Hematology Department at Fattouma Bourguiba Hospital in Monastir over a period of 14 years. Results: Thrombotic events related to ET were recorded in 18 patients (24.3%) in our series. They led to the diagnosis of ET in 14.9% of cases and occurred during follow-up in 9.4% of cases. Thrombosis was arterial in 55.6% of cases, mostly cerebral (70%). It was venous in 44.4% of cases, affecting mainly deep veins and mesenteric veins (37.5% of cases each). Four cases (5.4%) of thrombotic complications of unusual sites were noted, involving the splanchnic venous system in 3 cases and the cerebral venous system in one case. No significant association was found between the risk group and the occurrence of thrombotic complications regardless of the score used to assess thrombotic risk (ELN score, IPSET score and revised IPSET score). As for hemorrhagic complications, a total of 13 (17.5%) hemorrhagic events related to ET were recorded in our series. Four percent of them led to the diagnosis of ET and 13.5% occurred during follow-up. They were mostly (61.5%) mucocutaneous. Four percent of these hemorrhagic events were severe by location (2 cases of muscle hematoma and 1 case of retinal hemorrhage). Summary/Conclusion: In our series, the frequency of ET-related hemorrhagic complications was consistent with the literature data. However, the frequency of thrombosis was lower than that reported in other series. The thrombotic risk group was not a reliable predictor of the occurrence of thrombotic events in our patients. Keywords: Arterial thrombosis, Venous thrombosis, Thrombocythemia, Hemorrhage
PB2322: MULTIPLE PRIMARY TUMORS IN PATIENTS WITH NON-HODGKIN’S LYMPHOMA: A RETROSPECTIVE SINGLE-CENTER STUDY
Authors: Lusine Sahakyan, Lusine Harutyunyan, Marine Melik-Andreasyan, Alvard Poghosyan, Astghik Voskanyan, Samvel Danelyan, Narine Ghazaryan
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: The occurrence of multiple primary malignant tumors (MPMT) is known to be present in some instances of non-Hodgkin’s lymphoma (NHL). Aims: Our current study examines the frequency of MPMT in NHL patients in Armenia, including their clinical features and overall patient survival rates. Methods: The data of 2026 patients with NHL were analyzed. The patients were diagnosed between January 2010 and December 2021 at Hematology Center after Prof. R. Yeolyan of Armenia Results: Out of the 24 patients diagnosed with MPMT, 19 had synchronous MPMT (sMPMTs), and 5 had metachronous MPMT (mMPMTs). The majority (70%) of patients with MPMT were male, aged >50 years. The most common types of lymphoma among patients with MPMT were diffuse large B-cell lymphoma (DLBCL) and T-cell non-Hodgkin’s lymphoma (T-NHL). Some patients with MPMT had multiple hematological diagnoses, such as T-NHL and Hodgkin’s lymphoma, or DLBCL with myelofibrosis. Solid cancer’s most commonly affected sites were the organs of the gastrointestinal tract (33%) and the mammary gland (33%). The study found that patients with synchronous MPMT had higher overall survival rates than those with metachronous MPMT. However, compared to patients without MPMT, the prognosis for NHL patients with MPMT was slightly worse, with a 5-year overall survival rate of 68.9% and 76.1% (P = 0.042), respectively. Among patients with adenocarcinoma, the cumulative mortality rate from solid tumors was significantly higher in patients with MPMT than in patients without MPMT. The treatment sequence was chosen based on the severity of NHL and solid tumor։ which required immediate chemotherapy. Summary/Conclusion: When evaluating patients before treatment, it is essential always to consider the possibility of the existence of MPMT. Managing patients with MPMT and NHL, a rare disease, requires a clear protocol and an individualized approach to therapy. Keywords: Diffuse large B cell lymphoma, Survival, NHL
PB2050: COMPARISON OF CLINICAL CHARACTERISTICS OF CHILD AND ADULT PATIENTS WITH PNH: ——TEN-YEAR FOLLOW-UP
Authors: Hui Yang, Jin LI, Yueming Gong, Ninning Wang, Haiying Hua, Xiaoyu Chen, Ting Zhang, Guangsheng He, Jianyong LI
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic stem cell disease, characterized by intravascular hemolytic anemia, thrombophilia and bone marrow failure. Compared with adults, PNH is less likely to occur in children. Aims: The study aimed to clarify the demographic and clinical characteristics of children with PNH compared with adults. Methods: This study retrospectively compared the demographic features, PNH classification and thrombotic events of 23 child and 67 adult PNH patients, and evaluated the blood and hemolytic indexes, organ function status and survival. This retrospective study was conducted by the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100050945) from May 2014 to July 2020, including five centers: the First Affiliated Hospital with Nanjing Medical University (Nanjing, China), Affiliated Hospital of Jiangnan University (Wuxi, China), Nanjing Jiangning Hospital (Nanjing, China), the Second Hospital of Nanjing (Nanjing, China) and the Second Hospital of Anhui Medical University (Hefei, China). Results: The two groups didn’t show differences in gender (p=0.817) and PNH classification (p=0.238), including classic PNH (56.52% vs 71.64%, p=0.181), PNH combined bone marrow disease (BMD) (34.78% vs 25.37%, p=0.385), or subclinical PNH (8.70% vs 2.99%, p=0.269) (Table 1). Thrombosis events (13.04% vs 8.96%, p=0.688), D-dimer level (0.34mg/L vs 0.39mg/L, p=0.963), reticulocyte percentage (4.65% vs 5.14%, p=0.089), hemoglobin level (66 g/L vs 72 g/L, p=0.601), neutrophil count (2×109/L vs 2.06×109/L, p=0.978), platelet count (95×109/L vs 104 ×109/L, p=0.526), lactate dehydrogenase level (790 U/L vs 1010 U/L, p=0.407), and indirect bilirubin level (12μmol/L vs 18.2μmol/L, p=0.177) were comparable in two groups (Table 1). The proportion of patients in hemolytic state (LDH＞1.5×ULN) was also similar (p=0.241). Creatinine level and PNH clone size in children group were lower than those in adult group (47.9 μmol/L vs 61 μmol/L, p=0.031) (63.3% vs 86.9%, p=0.023). None with pulmonary hypertension was found in PNH children group, while 8 cases in adult group had mild pulmonary hypertension (p=0.009). The survival rate of PNH patients in children and adults were similar during the 10-year follow-up (92.9% vs 92.6%，P=0.968). Summary/Conclusion: Our study demonstrated PNH patients in children and adults both experienced similar clinical characteristics of hemolysis, thrombosis and cytopenia, but adult patients had larger PNH clone, higher creatinine levels and percentage of pulmonary hypertension.Keywords: Pulmonary hypertension, Children, Adult, Paroxysmal nocturnal hemoglobinuria (PNH)
PB2371: MCP-1-CCR2-M2 MACROPHAGES AXIS CONTRIBUTES TO DIFFUSE LARGE B-CELL LYMPHOMA PROGRESSION AND INHIBITS ANTITUMOR IMMUNE RESPONSE
Authors: Yan-LI LI, Zhao-Feng Wen, Qi-Tang Huang, Quan-Quan Hu
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematological malignancy with restricted effective therapy choices. The MCP-1/CCR2 axis is required for the recruitment of monocytes and polarization of macrophages. Aims: We firstly revealed MCP-1, CCR2, CD68 and CD163 expression were respectively positively related with poor prognosis in DLBCL in our previous work. Now, we further investigated the feasibility of treatment targeting MCP-1-CCR2-macrophages axis in DLBCL. Methods: MCP-1, CD68, CD163 expression was analyzed by immunohistochemistry in 143 DLBCL patients tissues, and MCP-1 concentration and CD14+CCR2+ monocytes in peripheral blood were analyzed in another cohort by enzyme linked immunosorbent assay or flow cytometry. THP-1 or U937 cells were used to mimic macrophages polarization with or without the blockade of MCP-1/CCR2 axis in vitro. BALB/C mice subcutaneous tumors were evaluated and detected after blocking MCP-1/CCR2 axis with CCR2 antagonist. Results: MCP-1, CD68, CD163 expression and proportion of CD14+CCR2+ monocytes in peripheral blood are prognostic for DLBCL patients. MCP-1 expression is positively associated with CD68 or CD163 expression in DLBCL. Blockade of MCP-1/CCR2 axis with CCR2 antagonist inhibits monocytes recruitment and M2 macrophages polarization in vitro. Further, the subcutaneous tumors growth is suppressed after blocking MCP-1/CCR2 axis with CCR2 antagonist by decreasing the amount of M2 tumor-associated macrophages (TAMs) while increasing the amount of CD8+ T cells. Summary/Conclusion: MCP-1-CCR2-M2 macrophages polarization plays vital roles in DLBCL progression. Blockade of MCP-1/CCR2 axis with CCR2 antagonist suppresses DLBCL progression by reversing M2 macrophages polarization and activating CD8+ T cell antitumor immune response. The results demonstrate the translational potential of MCP-1/CCR2 blockade for treatment of DLBCL. Keywords: Diffuse large B cell lymphoma, CD8 T cells, Macrophage
PB1832: INFLAMMATION INDUCED COAGULATION IN ACUTE MYELOID LEUKEMIA
Authors: Olivera Mitrović Ajtić, Dragoslava Djikić, Nada Suvajdžić-Vuković, Mirjana Mitrovic, Tijana Subotički, Milica Vukotić, Teodora Dragojević, Miloš Diklić, Nikola Pantić, Vladan Čokić
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Patients with acute myeloid leukemia (AML) have an increased risk of thrombotic complications in the range of 4.2 - 5.2%. Aims: Our hypothesis is that inflammation is responsible for deterioration of coagulation in AML. Methods: Quantification of neutrophil extracellular traps (NETs) from peripheral blood of patients with AML by measurement of circulating cell-free DNA (cfDNA) and myeloperoxidase (MPO) activity. Inflammatory cytokines, coagulation factors and chemokines are measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry in peripheral blood, while fibrinolytic activity with fluorescent tissue-type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) assays. Results: The pro-inflammatory cytokines IL-1β and TNF-α were significantly increased in AML, but not the chemokines IL-8 and MCP-1. NETs were increased in the peripheral blood of patients with AML (p<0.05) as measured by cfDNA and MPO activity. Regarding coagulation, factor VIII (p<0.05) and adhesion molecule P-selectin (p<0.001) were increased in plasma. Fibrinolytic activity was 3-fold decreased in the plasma of patients with AML (p<0.01) as measured by tPA. In contrast, uPA levels were increased in patients with AML (p<0.05). Tissue factor (CD142+) inflammatory microparticles derived from monocytes (CD14+: 5.1±0.6, p<0.001), activated monocytes (CD14+/CD16+: 2.89±0.4%, p<0.05) and circulating endothelial cells (CD31+/CD144+: 4.08±0.5%, p<0.05) were increased in AML compared to healthy controls. Summary/Conclusion: Chronic inflammation is present in AML in parallel with reduced fibrinolysis and increased coagulation provoking the risk of thrombosis. A panel of the applied inflammatory/ procoagulant biomarkers can be used as a predictor of thrombosis in AML. Keywords: Acute myeloid leukemia, Coagulation, Inflammation, Fibrinolysis